Program Project grant

基本的假设是，椎间盘退变会导致下腰痛，而 这种更新的第二个假设，即退化过程是可以防止、延缓或修复的 保留计划项目拨款。正在进行的方案项目赠款的四个项目构成了这一点的基础 竞争性更新申请，并实现了对生物力学和 参与椎间盘退变的代谢因素。项目1开发了一种新的精密和 测量腰椎节段性运动的重复性非侵入性三维分析方法。项目 2建立并验证了一个有限元模型，该模型包括了流体的流动和孔隙的弹性行为。 腰间盘。项目3确定了胶原蛋白、蛋白多糖和基质降解的生化变化。 椎间盘中与衰老和/或组织退化有关的酶。 项目4建立了兔急性或亚急性腰椎间盘退变环状穿刺术模型 结果表明，随着椎间盘高度的恢复，注射生长因子可上调基质合成。在……里面 在这个更新方案中，我们设计了机械性的、假设驱动的和潜在的实验 进一步促进我们对相关生物力学和生物因素的理解 并伴有椎间盘退变。项目1将测量扭转和屈曲伸展时的运动性超活动能力 并将这些数据与下腰痛症状相关联。影响预后的重要因素 椎间盘和小关节退变的进展和症状将被识别。项目2将重点放在 开发一个更接近于退变椎间盘的有限元模型，并将研究其 对重复加载的响应。项目3将确定以下方面的行动机制和相互作用 生长因子、细胞因子和不同调节分子在椎间盘组织内稳态中的作用及其潜力 用于促进椎间盘组织修复。项目4将确定椎间盘退变是否可以延缓或逆转 通过控制合成代谢和分解代谢途径之间的平衡，以及如果营养运输受到损害 通过终板限制应用生长因子诱导的细胞介导的椎间盘修复。这 计划项目将带来重大进展，这将直接转化为许多人的解脱 患有与腰间盘和小关节退变相关的下腰痛。

The underlying primary hypothesis, that intervertebral disc degeneration contributes to low back pain, and a second hypothesis, that the process of degeneration can be prevented, retarded or repaired, of this renewal Program Project Grant remain. The four projects of the ongoing Program Project Grant form the basis for this competitive renewal application and have achieved an improved understanding of the biomechanical and metabolic factors involved in intervertebral disc degeneration. Project 1 developed a new precise and reproducible non-invasive 3-D analysis method of measuring segmental motion of the lumbar spine. Project 2 developed and validated a finite element model, which includes fluid flow and the poro-elastic behavior of the intervertebral disc. Project 3 identified biochemical changes in collagens, proteoglycans, and matrixdegrading enzymes in the intervertebral disc that are associated with aging and/or tissue degeneration. Project 4 developed an annular puncture rabbit model of acute or sub-acute intervertebral disc degeneration and showed that the injection of growth factor up-regulates matrix synthesis with restoration of disc height. In this renewal proposal, we have designed experiments that are mechanistic, hypothesis-driven and potentially translational to further advance our understanding of the biomechanical and biological factors associated with intervertebral disc degeneration. Project 1 will measure kinematic hypermobility in torsion and flexionextension in vivo and correlate those data with low back pain symptoms. Factors of prognostic importance to the progression of disc and facet joint degeneration and symptoms will be identified. Project 2 will focus on developing a finite element model that more closely corresponds to a degenerative disc and will study its response to repetitive loading. Project 3 will determine the mechanism of action and interplay between growth factors, cytokines and different regulatory molecules in disc tissue homeostasis and their potential use in promoting disc tissue repair. Project 4 will determine if disc degeneration can be delayed or reversed by manipulating the balance between anabolic and catabolic pathways and if compromised nutrient transport through the endplate limits cell-mediated disc repair induced by the application of a growth factor. This Program Project will result in major progress that will directly translate into relief for so many individuals suffering from low back pain that is associated with intervertebral disc and facet joint degeneration.